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Title: microRNA profiling by array of human A375 cells treated with 20 uM of reverse transcriptase inhibitor efavirenz      
dateReleased:
01-01-2014
description:
Background: LINE-1 elements make up the most abundant retrotransposon family in the human genome. Full-length LINE-1 elements encode their own reverse transcriptase (RT). They are expressed at low levels in normal cells and abundantly in cancer cells. RT down-regulation, by either RNA interference to LINE-1 elements, or by RT inhibitory drugs, was previously found to reduce proliferation and promote differentiation in cancer cells and to antagonize tumor growth in animal models. Results: We report that the RT inhibitor efavirenz effectively inhibit proliferation of a variety of human tumorigenic cell lines while only slightly affecting the proliferation of human normal fibroblast cell line, a difference that nicely matches RT expression in the former cell lines and its lack in the latter. The finding of Alu and LINE-1 containing DNA:RNA hybrid molecules - identified by CsCl density gradients - selectively in cancer but not in normal cells, suggests that RNA transcripts from these retroelements are candidate substrates for reverse transcription. These hybrids disappear in tumor cells treated with efavirenz, under the same conditions which induce an extensive reprogrammed expression profiles for protein-coding genes, microRNAs (miRNAs) and ultraconserved regions (UCRs). The RT-sensitive miRNAs and UCRs are significantly associated with Alus sequences. Conclusions: A novel RT-dependent mechanism governs the balance between single-stranded and double-stranded RNA production. In cancer cells, the abundant LINE-1-encoded RT reverse-transcribes retroelement-derived mRNAs, generating RNA:DNA hybrids. We propose that this impairs the formation of double-stranded RNAs and the ensuing production of small regulatory RNAs, with a direct impact on gene expression. RT inhibition restores the ‘normal’ small RNA profile and the regulatory networks that depend on them. Thus, the retrotransposon-encoded RT drives an epigenetic mechanism crucial to maintenance of the transformed state in tumor cells.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-MTAB-1737
refinement:
raw
keywords:
functional genomics
dateModified:
06-03-2014
creators:
Manuela Ferracin
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-MEXP-1663
name:
Agilent Human miRNA G4470B (019118)
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-1737/E-MTAB-1737.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-1737/E-MTAB-1737.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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